1. Academic Validation
  2. Allosteric adenosine receptor modulation reduces hypersensitivity following peripheral inflammation by a central mechanism

Allosteric adenosine receptor modulation reduces hypersensitivity following peripheral inflammation by a central mechanism

  • J Pharmacol Exp Ther. 2003 Jun;305(3):950-5. doi: 10.1124/jpet.102.047951.
Xinhui Li 1 Dawn Conklin Hui-Lin Pan James C Eisenach
Affiliations

Affiliation

  • 1 Department of Anesthesiology and Center for the Study of Pharmacologic Plasticity in the Presence of Pain, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157-1009, USA. xli@wfubmc.edu
Abstract

Activation of adenosine A1 receptors by endogenous adenosine or synthetic agonists produces antinociception in animal models of acute pain and also reduces hypersensitivity in models of inflammatory and nerve-injury pain. Allosteric adenosine modulators facilitate and potentiate the action of adenosine agonists at the A1 receptors. The purpose of the current study was to examine the effect and site of action for an allosteric adenosine modulator, T62 [2-amino-3-(4-chlorobenzoyl)-5,6, 7,8-tetrahydrobenzothiophene], in rat models of acute pain and inflammation. Intrathecal (i.t.) T62 did not change the withdrawal latency or threshold of normal rats to acute heat or to acute paw pressure. In contrast, i.t. T62 reversed thermal hypersensitivity in carrageenin-inflamed rats. Subcutaneous (s.c.) injection of T62 into the inflamed paw had no such effect. To investigate a potential site of action on nociceptors, single-unit afferent activity to mechanical stimuli on A delta- and C-fibers was examined in normal or carrageenin-inflamed rats before and after intravenous (i.v.) T62 administration. Intravenous T62, 3 mg/kg, had no significant effect in either normal or inflamed conditions. These results support previous studies to suggest that Adenosine Receptor modulators lack efficacy to acute nociceptive stimuli in the normal condition, but reduce hypersensitivity during inflammation through a central mechanism.

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